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Abstract:

Transcription factor codes play an essential role in neuronal specification and axonal guidance in both vertebrate and
invertebrate organisms. However, how transcription codes regulate axon pathfinding remains poorly understood. One such code
defined by the homeodomain transcription factor Even-skipped (Eve) and by the GATA 2/3 homologue Grain (Grn) is specifically
required for motor axon projection towards dorsal muscles in
Drosophila
. Using different mutant combinations, we present
genetic evidence that both Grn and Eve are in the same pathway as Unc-5 in dorsal motoneurons (dMNs). In
grn
mutants, in
which dMNs fail to reach their muscle targets, dMNs show significantly reduced levels of
unc-5
mRNA expression and this
phenotype can be partially rescued by the reintroduction of
unc-5
. We also show that both
eve
and
grn
are required
independently to induce expression of
unc-5
in dMNs. Reconstitution of the
eve
-
grn
transcriptional code of a dMN in dMP2
neurons, which do not project to lateral muscles in
Drosophila
, is able to reprogramme those cells accordingly; they robustly
express
unc-5
and project towards the muscle field as dMNs. Each transcription factor can independently induce
unc-5
expression
but
unc-5
expression is more robust when both factors are expressed together. Furthermore, dMP2 exit is dependent on the level
of
unc-5
induced by
eve
and
grn
. Taken together, our data strongly suggests that the
eve
-
grn
transcriptional code controls axon
guidance, in part, by regulating the level of
unc-5
expression